State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100093, China.
Dev Cell. 2022 Nov 7;57(21):2469-2482.e5. doi: 10.1016/j.devcel.2022.10.001. Epub 2022 Oct 28.
Mitochondrial perturbations within neurons communicate stress signals to peripheral tissues, coordinating organismal-wide mitochondrial homeostasis for optimal fitness. However, the neuronal control of the systemic stress regulation remains poorly understood. Here, we identified a G-protein-coupled receptor (GPCR), SRZ-75, that couples with Gαq signaling in a pair of chemosensory ADL neurons to drive the mitochondrial unfolded protein response (UPR) activation in the intestine via the release of neuropeptides in Caenorhabditis elegans. Constitutive activation of Gαq signaling in the ADL neurons is sufficient to induce the intestinal UPR, leading to increased stress resistance and metabolic adaptations. Ablation of ADL neurons attenuates the intestinal UPR activation in response to various forms of neuronal mitochondrial dysfunction. Thus, GPCR and its Gαq downstream signaling in two sensory neurons coordinate the systemic UPR activation, representing a previously uncharacterized, but potentially conserved, neuronal signaling for organismal-wide mitochondrial stress regulation.
神经元内的线粒体扰动将应激信号传递到外周组织，协调全身线粒体动态平衡以实现最佳适应度。然而，神经元对系统应激调节的控制仍知之甚少。在这里，我们鉴定了一种 G 蛋白偶联受体 (GPCR)，即 SRZ-75，它在一对化学感觉 ADL 神经元中与 Gαq 信号偶联，通过在秀丽隐杆线虫中释放神经肽来驱动肠道中线粒体未折叠蛋白反应 (UPR) 的激活。ADL 神经元中 Gαq 信号的组成性激活足以诱导肠道 UPR，从而提高应激抗性和代谢适应。ADL 神经元的缺失会减弱对各种形式的神经元线粒体功能障碍的肠道 UPR 激活。因此，GPCR 及其在两个感觉神经元中的 Gαq 下游信号协调全身 UPR 的激活，代表了一种以前未被描述但可能保守的神经元信号，用于全身线粒体应激调节。
